TY - JOUR
T1 - Removal of a gadolinium based contrast agent by a novel sorbent hemoperfusion in a chronic kidney disease (CKD) rodent model
AU - Ngamcherdtrakul, Worapol
AU - Morry, Jingga
AU - Sangvanich, Thanapon
AU - Reda, Moataz
AU - Bejan, Daniel S.
AU - Fryxell, Glen E.
AU - Yantasee, Wassana
N1 - Funding Information:
This work was supported by the National Institute of General Medical Sciences (NIGMS, R01GM089918), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK, R41DK094571), the Oregon Nanoscience and Microtechnologies Institute (ONAMI), and OHSU’s Office of Vice President for Research (VPR) fund. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The authors are grateful to Jeff Creim, Dr. Charles Timchalk, and Dr. George Porter for their contribution. We are also thankful to Dr. Tania Vu for her independent review of the data in this paper as required by OHSU’s conflict of interest guidelines.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Gadolinium based contrast agents (GBCAs) have been linked to toxicity in patients, regardless of having impaired or normal renal function. Currently, no therapy is considered highly effective for removing gadolinium (Gd) from the body. We propose a new strategy to reduce blood Gd content that facilitates whole body removal of Gd using a hemoperfusion system consisting of a cartridge of porous silica beads (Davisil®) functionalized with 1,2-hydroxypyridinone (1,2-HOPO). Herein, we report optimization of the hemoperfusion system using an ex vivo blood and an in vivo rat model of chronic kidney disease (CKD). In our ex vivo system, 1,2-HOPO-Davisil outperformed Gambro activated charcoal (AC), which is commonly used in clinical hemoperfusion of aqueous toxins, in terms of Gd capture capacity and rate. In the CKD rat model, the 1,2-HOPO-Davisil hemoperfusion system removed Gd by 3.4 times over the Gambro AC system. 1,2-HOPO-Davisil did not change complete blood counts and common blood biochemistry. Thus, this strategy has great potential for clinical translation to manage GBCAs after magnetic resonance imaging (MRI), before Gd can deposit in the body and cause long-term toxicity. Although gadodiamide was used as a proof of concept model for GBCAs in this study, 1,2-HOPO functionalized mesoporous silica could also capture dissociated Gd and other GBCAs.
AB - Gadolinium based contrast agents (GBCAs) have been linked to toxicity in patients, regardless of having impaired or normal renal function. Currently, no therapy is considered highly effective for removing gadolinium (Gd) from the body. We propose a new strategy to reduce blood Gd content that facilitates whole body removal of Gd using a hemoperfusion system consisting of a cartridge of porous silica beads (Davisil®) functionalized with 1,2-hydroxypyridinone (1,2-HOPO). Herein, we report optimization of the hemoperfusion system using an ex vivo blood and an in vivo rat model of chronic kidney disease (CKD). In our ex vivo system, 1,2-HOPO-Davisil outperformed Gambro activated charcoal (AC), which is commonly used in clinical hemoperfusion of aqueous toxins, in terms of Gd capture capacity and rate. In the CKD rat model, the 1,2-HOPO-Davisil hemoperfusion system removed Gd by 3.4 times over the Gambro AC system. 1,2-HOPO-Davisil did not change complete blood counts and common blood biochemistry. Thus, this strategy has great potential for clinical translation to manage GBCAs after magnetic resonance imaging (MRI), before Gd can deposit in the body and cause long-term toxicity. Although gadodiamide was used as a proof of concept model for GBCAs in this study, 1,2-HOPO functionalized mesoporous silica could also capture dissociated Gd and other GBCAs.
UR - http://www.scopus.com/inward/record.url?scp=85060548523&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85060548523&partnerID=8YFLogxK
U2 - 10.1038/s41598-018-37348-2
DO - 10.1038/s41598-018-37348-2
M3 - Article
C2 - 30679698
AN - SCOPUS:85060548523
VL - 9
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 709
ER -